Full length articleThe PFOS disturbed immunomodulatory functions via nuclear Factor-κB signaling in liver of zebrafish (Danio rerio)
Introduction
Perfluorooctane sulfonate (PFOS), a fluorinated organic compound, has been widely used in a range of industrial and commercial applications for many years, such as wetting agents, fire retardants, stain resistant treatments for leather and carpets, cosmetics, components of pharmaceuticals and insecticides [1,2]. Due to the properties of global distribution, persistence, high bioaccumulation and negligible elimination, PFOS has been widely recognized as a man-made persistent organic pollutant and been found in the organisms and environment in the world [[3], [4], [5]]. PFOS is mostly found in the environment in relatively low concentrations (around the ng/L range) [6]. For example, PFOS concentrations ranged from below 10 pg/L to 703 ng/L in surface water of ocean, coastal areas, and river estuaries [7,8]. However, the concentration of PFOS can up to 2260 μg/L after an accidental release of fire fighting foam [9] and the levels in waste water and nearby river system of a semiconductor fabrication plant could reach 12,566 mg/L and 5.4 mg/L, respectively [10]. Meanwhile, PFOS has been demonstrated to accumulate in aquatic organisms [11,12]. The maximum concentrations of PFOS detected in the liver were up to 1.8–9.03 μg/g and 72.9 μg/g in some fish species from Tokyo bay, Flanders and an accidental spill site [9,11,13]. The PFOS levels in various edible fish muscles ranged from 0.27 ng/g to 5.98 ng/g wet weight [14,15].
PFOS could result in a series of adverse effects in aquatic organisms, such as hepatotoxicity and disturbance of DNA metabolism homeostasis, reproductive and developmental toxicity, disturbed lipid metabolism, induction of oxidative stress and apoptosis, the opening of the tight junction [[16], [17], [18], [19], [20], [21]]. Despite the toxicity and biological effects on aquatic organisms, very few studies have been investigated on the toxicity of PFOS on immune system and the underlying molecular mechanisms involved in its toxicity.
It is widely accepted that PFOS has estrogenic and endocrine disrupting effects [22,23]. PFOS could cause estrogenic effects that could disturb the expressions of estrogenic-related genes, and thus result in the developmental and reproductive abnormalities in some teleost fish [22,24,25]. PFOS had disruptive endocrine effects through the peroxisome proliferators-activated receptors (PPARs) in fish [26], which could regulate the energy homeostasis, cell proliferation, differentiation and survival. The immune system serves as a potential target for endocrine disrupters, especially environmental estrogens [27]. More and more studies suggested that endocrine disrupting chemicals could interfere with the gene expressions related to the innate immune system during the early developmental stages of zebrafish (Danio rerio) and that the increased levels of estrogen could contribute to a decreased anti-viral immune response, causing pregnancy-associated morbidities in mice [28]. It is generally recognized that PFOS exposure could change the immune process in some experimental biological models [16,29].
Inflammation is one of the first responses of the immune system after being exposed to exogenous chemicals, which might play a very important role in the diseases’ development [30]. More and more evidence indicated that expressions of the inflammatory related genes play an important role in the functional capacity of the immune system, such as the pro-inflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), which both increased in the brains of rat pups after prenatal exposure to PFOS [31]. However, few studies have investigated the toxic effects of PFOS on immune toxicity in gene expression profiles in aquatic organisms, and the underlying molecular mechanisms involved have not been clarified.
Zebrafish (Danio retrio) are widely used as an important ecological toxicological model to measure the environmental pollutants based on its advantages, including small size, high reproductive performance, rapid organogenesis, morphological and physiological similarities to mammals, high sensitivity to the harmful substances [32]. Previous studies have showed that zebrafish were used to evaluate the immunization toxicity of chemicals in the laboratory [[33], [34], [35], [36]]. In the present study, to remove sex as a factor/variable, the effects of waterborne PFOS on the growth performance, histological changes, the levels of ROS, the activities of immune-related enzymes and the transcriptional profiles of immune-related genes were examined in the liver of male zebrafish exposed to different concentrations of 0, 0.02, 0.04 and 0.08 mg/L of PFOS or cotreatment with PFOS and PDTC to investigate the effects of PFOS on immune system and the underlying toxic mechanisms caused by PFOS.
Section snippets
Test animals and chemicals
Adult male zebrafish three months old (Danio rerio) (AB strain), with mean body weight and body length of 0.19 ± 0.03 g and 2.5 ± 0.3 cm, were obtained from Taiyuan fish hatcheries in Shanxi Province, PR China. They were kept in a flow-through system with dechlorinated tap water (pH, 7.0–7.4; water temperature, 28 ± 1 °C; light regime, 14-h light and 10-h dark) for 15 days to acclimate to laboratory conditions before exposure, and the death rate is less than 1%. Zebrafish were fed with
PFOS concentration in livers
PFOS concentrations in livers were below determination limit in the control group during the exposure. PFOS accumulated in livers after exposure, and remarkably elevations were found in three exposure groups compared with the control group at three stages. After 7 d of exposure, PFOS levels in livers reached 2.40 ± 0.18, 3.72 ± 0.41, 5.07 ± 0.24 μg/g wet weight for the exposure groups of 0.02, 0.04, 0.08 mg/L, respectively. After exposure for 14 and 21 d, the levels were 7.19 ± 0.28,
Discussion
The immune system is a host defense system that protects against many physical and chemical factors even disease. Usually, the changes induced by chemical toxic agent occur earlier than other toxic symptoms. The liver of fish is the most important detoxification organ, and the most important target organ when the fish is infected by the external poison. Many studies have shown that PFOS has an adverse effect on liver of fish [22,[39], [40], [41]]. As a result, we continuously exposed zebrafish
Conclusions
In summary, this study explored the effects of PFOS on growth performance, histopathology, immune-related enzymes and the expressions of immune-related genes in liver. Our results clearly demonstrated FPOS exposure could significantly inhibit the growth of male zebrafish. Moreover, FPOS could disturb immunomodulatory functions on liver of male zebrafish by changing the normal structure of liver, disturbing the activities of immune-related enzymes, and a series of gene transcriptions involved in
Conflicts of interest
The authors declare that there are no conflicts of interest.
Acknowledgments
This work was supported by funding from the National Natural Science Foundation of China (31440087; 31502141); the China Postdoctoral Science Foundation (2012M520601; 2013T60267); the Doctor Initial Funding of Shanxi Agricultural University(XB2009003); the Postdoctoral Science Foundation of Shanxi Agricultural University (92462); National Training Program of Innovation and Entrepreneurship for Undergraduates (201610113026); Undergraduate Training Program for Innovation and Entrepreneurship of
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Jinshu Guo and Panhong Wu contributed equally to this work.